Abstract
MicroRNAs (miRNAs)-based therapies hold great promise for cancer treatment, challenges such as expression variability, off-target effects, and limited clinical effectiveness have led to the withdrawal of many clinical trials. This review investigates the setbacks in miRNA-based therapies by examining miR-21, miR-34, and miR-155, highlighting their functional complexity, off-target effects, and the challenges in delivering these therapies effectively. Moreover, It highlights recent advances in delivery methods, combination therapies, and personalized treatment approaches to overcome these challenges. This review highlights the intricate molecular networks involving miRNAs, particularly their interactions with other non-coding RNAs, such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), emphasizing the pivotal role of miRNAs in cancer biology and therapeutic strategies. By addressing these hurdles, this review aims to steer future research toward harnessing the potential of miRNA therapies to target cancer pathways effectively, enhance anti-tumor responses, and ultimately improve patient outcomes in precision cancer therapy.